Lopinavir

Lopinavir
Clinical data
Other names	ABT-378
AHFS/Drugs.com	International Drug Names
MedlinePlus	a602015
License data	EU EMA: by INN;
Routes of; administration	By mouth
ATC code	J05AR10 (WHO) (with ritonavir);
Legal status
Legal status	UK: POM (Prescription only); US: ℞-only;
Pharmacokinetic data
Bioavailability	Unknown
Protein binding	98-99%
Metabolism	Hepatic
Elimination half-life	5 to 6 hours
Excretion	Mostly fecal
Identifiers
	IUPAC name (2S)-N-[(2S,4S,5S)-5-[2-(2,6-dimethylphenoxy)acetamido]-4-hydroxy-1,6-diphenylhexan-2-yl]-3-methyl-2-(2-oxo-1,3-diazinan-1-yl)butanamide;
CAS Number	192725-17-0 ;
PubChem CID	92727;
DrugBank	DB01601 ;
ChemSpider	83706 ;
UNII	2494G1JF75;
KEGG	D01425 ;
ChEMBL	ChEMBL729 ;
CompTox Dashboard (EPA)	DTXSID8046456 ;
ECHA InfoCard	100.281.362
Chemical and physical data
Formula	C37H48N4O5
Molar mass	628.814 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES O=C(N[C@@H](Cc1ccccc1)[C@@H](O)C[C@@H](NC(=O)[C@@H](N2C(=O)NCCC2)C(C)C)Cc3ccccc3)COc4c(cccc4C)C;
	InChI InChI=1S/C37H48N4O5/c1-25(2)34(41-20-12-19-38-37(41)45)36(44)39-30(21-28-15-7-5-8-16-28)23-32(42)31(22-29-17-9-6-10-18-29)40-33(43)24-46-35-26(3)13-11-14-27(35)4/h5-11,13-18,25,30-32,34,42H,12,19-24H2,1-4H3,(H,38,45)(H,39,44)(H,40,43)/t30-,31-,32-,34-/m0/s1 ; Key:KJHKTHWMRKYKJE-SUGCFTRWSA-N ;
	(verify)

Lopinavir is an antiretroviral of the protease inhibitor class. It is used against HIV infections as a fixed-dose combination with another protease inhibitor, ritonavir (lopinavir/ritonavir).^[1]

It was patented in 1995 and approved for medical use in 2000.^[2]

Side effects

Side effects, interactions, and contraindications have only been evaluated in the drug combination lopinavir/ritonavir.

Pharmacology

Lopinavir is highly bound to plasma proteins (98–99%).^[3]

Reports are contradictory regarding lopinavir penetration into the cerebrospinal fluid (CSF). Anecdotal reports state that lopinavir cannot be detected in the CSF; however, a study of paired CSF-plasma samples from 26 patients receiving lopinavir/ritonavir found lopinavir CSF levels above the IC₅₀ in 77% of samples.^[4]

Research

A 2014 study indicates that lopinavir is effective against the human papilloma virus (HPV). The study used the equivalent of one tablet twice a day applied topically to the cervices of women with high-grade and low-grade precancerous conditions. After three months of treatment, 82.6% of the women who had high-grade disease had normal cervical conditions, confirmed by smears and biopsies.^[5] In 2020 lopinavir/ritonavir was found not to work in severe COVID-19. In this trial the medication was started typically around 13 days after the start of symptoms.^[6]

Lopinavir is found to inhibit MERS-CoV replication in the low-micromolar range in cell cultures.^[7]

References

^ "FDA Approved Drug Products: Kaletra". Retrieved 30 April 2004.
^ Fischer, Jnos; Ganellin, C. Robin (2006). Analogue-based Drug Discovery. John Wiley & Sons. p. 510. ISBN 9783527607495.
^ KALETRA (lopinavir/ritonavir) capsules; (lopinavir/ritonavir) oral solution. Prescribing information. April 2009
^ Capparelli E, Holland D, Okamoto C, et al. (2005). "Lopinavir concentrations in cerebrospinal fluid exceed the 50% inhibitory concentration for HIV". AIDS. 19 (9).
^ HIV drug used to reverse effects of virus that causes cervical cancer University of Manchester, 17 February 2014.
^ Cao, Bin; Wang, Yeming; Wen, Danning; Liu, Wen; Wang, Jingli; Fan, Guohui; Ruan, Lianguo; Song, Bin; Cai, Yanping; Wei, Ming; Li, Xingwang; Xia, Jiaan; Chen, Nanshan; Xiang, Jie; Yu, Ting; Bai, Tao; Xie, Xuelei; Zhang, Li; Li, Caihong; Yuan, Ye; Chen, Hua; Li, Huadong; Huang, Hanping; Tu, Shengjing; Gong, Fengyun; Liu, Ying; Wei, Yuan; Dong, Chongya; Zhou, Fei; Gu, Xiaoying; Xu, Jiuyang; Liu, Zhibo; Zhang, Yi; Li, Hui; Shang, Lianhan; Wang, Ke; Li, Kunxia; Zhou, Xia; Dong, Xuan; Qu, Zhaohui; Lu, Sixia; Hu, Xujuan; Ruan, Shunan; Luo, Shanshan; Wu, Jing; Peng, Lu; Cheng, Fang; Pan, Lihong; Zou, Jun; Jia, Chunmin; Wang, Juan; Liu, Xia; Wang, Shuzhen; Wu, Xudong; Ge, Qin; He, Jing; Zhan, Haiyan; Qiu, Fang; Guo, Li; Huang, Chaolin; Jaki, Thomas; Hayden, Frederick G.; Horby, Peter W.; Zhang, Dingyu; Wang, Chen (18 March 2020). "A Trial of Lopinavir–Ritonavir in Adults Hospitalized with Severe Covid-19". New England Journal of Medicine. doi:10.1056/NEJMoa2001282.
^ de Wilde, Adriaan H.; Jochmans, Dirk; Posthuma, Clara C.; Zevenhoven-Dobbe, Jessika C.; van Nieuwkoop, Stefan; Bestebroer, Theo M.; van den Hoogen, Bernadette G.; Neyts, Johan; Snijder, Eric J. (August 2014). "Screening of an FDA-Approved Compound Library Identifies Four Small-Molecule Inhibitors of Middle East Respiratory Syndrome Coronavirus Replication in Cell Culture". Antimicrobial Agents and Chemotherapy. 58 (8): 4875–4884. doi:10.1128/AAC.03011-14.

External links

[1] "FDA Approved Drug Products: Kaletra". Retrieved 30 April 2004.

[Fis2006-2] Fischer, Jnos; Ganellin, C. Robin (2006). Analogue-based Drug Discovery. John Wiley & Sons. p. 510. ISBN 9783527607495.

[PInfo-3] KALETRA (lopinavir/ritonavir) capsules; (lopinavir/ritonavir) oral solution. Prescribing information. April 2009

[4] Capparelli E, Holland D, Okamoto C, et al. (2005). "Lopinavir concentrations in cerebrospinal fluid exceed the 50% inhibitory concentration for HIV". AIDS. 19 (9).

[5] HIV drug used to reverse effects of virus that causes cervical cancer University of Manchester, 17 February 2014.

[6] Cao, Bin; Wang, Yeming; Wen, Danning; Liu, Wen; Wang, Jingli; Fan, Guohui; Ruan, Lianguo; Song, Bin; Cai, Yanping; Wei, Ming; Li, Xingwang; Xia, Jiaan; Chen, Nanshan; Xiang, Jie; Yu, Ting; Bai, Tao; Xie, Xuelei; Zhang, Li; Li, Caihong; Yuan, Ye; Chen, Hua; Li, Huadong; Huang, Hanping; Tu, Shengjing; Gong, Fengyun; Liu, Ying; Wei, Yuan; Dong, Chongya; Zhou, Fei; Gu, Xiaoying; Xu, Jiuyang; Liu, Zhibo; Zhang, Yi; Li, Hui; Shang, Lianhan; Wang, Ke; Li, Kunxia; Zhou, Xia; Dong, Xuan; Qu, Zhaohui; Lu, Sixia; Hu, Xujuan; Ruan, Shunan; Luo, Shanshan; Wu, Jing; Peng, Lu; Cheng, Fang; Pan, Lihong; Zou, Jun; Jia, Chunmin; Wang, Juan; Liu, Xia; Wang, Shuzhen; Wu, Xudong; Ge, Qin; He, Jing; Zhan, Haiyan; Qiu, Fang; Guo, Li; Huang, Chaolin; Jaki, Thomas; Hayden, Frederick G.; Horby, Peter W.; Zhang, Dingyu; Wang, Chen (18 March 2020). "A Trial of Lopinavir–Ritonavir in Adults Hospitalized with Severe Covid-19". New England Journal of Medicine. doi:10.1056/NEJMoa2001282.

[7] Wilde, Adriaan H.; Jochmans, Dirk; Posthuma, Clara C.; Zevenhoven-Dobbe, Jessika C.; van Nieuwkoop, Stefan; Bestebroer, Theo M.; van den Hoogen, Bernadette G.; Neyts, Johan; Snijder, Eric J. (August 2014). "Screening of an FDA-Approved Compound Library Identifies Four Small-Molecule Inhibitors of Middle East Respiratory Syndrome Coronavirus Replication in Cell Culture". Antimicrobial Agents and Chemotherapy. 58 (8): 4875–4884. doi:10.1128/AAC.03011-14.

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